A detailed examination of the synthesis of functionalized 6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepines 4 is described. Base‐promoted aromatic nucleophilic substitution of 5‐allyl‐4,6‐dichloropyrimidines 1a–c with different N‐substituted anilines and indoline gave the corresponding aminolysis products 3a–p, which on acid‐promoted intramolecular Friedel–Crafts cyclization produced the target polysubstituted 6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepines 4a–p in moderate to very high yields.

The biological potential of compounds of the tricyclic dibenzo[b,e]azepine system has resulted in considerable synthetic efforts to develop efficient methods for the synthesis of new derivatives of this kind. (9RS,15RS)-9-Ethyl-11-methyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2-a]azepin-3(2H)-one, CHNOS, (I), crystallizes as a kryptoracemate with Z' = 2 in the space group P2, with one molecule each of the (9R,15R) and (9S,15S) configurations in the asymmetric unit, while (9RS,15RS)-9-ethyl-7,12-dimethyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2-a]azepin-3(2H)-one, CHNOS, (II), crystallizes with Z' = 1 in the space group C2/c. Ethyl (13RS)-2-chloro-13-ethyl-4-oxo-8,13-dihydro-4H-benzo[5,6]azepino[3,2,1-ij]quinoline-5-carboxylate, CHClNO, (III), exhibits enantiomeric disorder in the space group P-1 such that the reference site is occupied by the 13R and 13S enantiomers, with occupancies of 0.900 (6) and 0.100 (6). In each of the two independent molecules in (I), the five-membered ring adopts an envelope conformation, but the corresponding ring in (II) adopts a half-chair conformation, while the six-membered ring in the major form of (III) adopts a twist-boat conformation. The conformation of the seven-membered ring in each of (I), (II) and the major form of (III) approximates to the twist-boat form. The molecules of compound (I) are linked by two C-H...O hydrogen bonds to form two independent antiparallel C(5) chains, with each type containing only one enantiomer. These chains are linked into sheets by two C-H...π(arene) hydrogen bonds, in which the two donors are both provided by the (9R,15R) enantiomer and the two acceptor arene rings form part of a molecule of (9S,15S) configuration, precluding any additional crystallographic symmetry. The molecules of compound (II) are linked by inversion-related C-H...π(arene) hydrogen bonds to form isolated cyclic centrosymmetric dimers. The molecules of compound (III) are linked into cyclic centrosymmetric dimers by C-H...O hydrogen bonds and these dimers are linked into chains by a π-π stacking interaction. Comparisons are made with some related structures.

Synthesis of Pyrimidine-Fused Benzazepines from 5-Allyl-4,6-dichloropyrimidines. -The new title benzazepines are synthesized by base-promoted aromatic nucleophilic substitution of pyrimidines (I) with different N-substituted anilines or indoline followed by acid-promoted intramolecular Friedel-Crafts cyclization. -(ACOSTA-QUINTERO, L. M.; JURADO, J.; NOGUERAS, M.; PALMA*, A.; COBO, J.; Eur. J. Org. Chem. 2015, 24, 5360-5369, http://dx.

Considering the importance of quinolones due to their broad spectrum of biological activities, the crystal structure of the title compound, C22H21NO3·0.5C7H16, has been determined. Two enantiomers of the benzazepinoquinoline molecule and one molecule of heptane form the asymmetric unit of this centrosymmetric triclinic (P\overline{1}) crystal. All the molecules in the crystal present disorder. Substitutional disorder is observed for the benzazepine molecules, where a minority conformer of the R enantiomer replaces the main conformer of the S enantiomer and vice versa. Positional disorder is found for the heptane solvent molecule, which occupies a void left by the independent enantiomers of both conformers.

A concise, efficient and versatile synthesis of amino-substituted benzo[b]pyrimido[5,4-f]azepines is described: starting from a 5-allyl-4,6-dichloropyrimidine, the synthesis involves base-catalysed aminolysis followed by intramolecular Friedel-Crafts cyclization. Four new amino-substituted benzo[b]pyrimido[5,4-f]azepines are reported, and all the products and reaction intermediates have been fully characterized by IR, H andC NMR spectroscopy and mass spectrometry, and the molecular and supramolecular structures of three products and one intermediate have been determined. In each of N,2,6,11-tetramethyl-N-phenyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepin-4-amine, CHN, (III), 4-(1H-benzo[d]imidazol-1-yl)-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine, which crystallizes as a 0.374-hydrate, CHN·0.374HO, (VIIIa), and 6,7,9,11-tetramethyl-4-(5-methyl-1H-benzo[d]imidazol-1-yl)-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine, CHN, (VIIIc), the azepine ring adopts a boat conformation, but with a different configuration at the stereogenic centre in (VIIIc), as compared with (III) and (VIIIa). In the intermediate 5-allyl-6-(1H-benzo[d]imidazol-1-yl)-N-methyl-N-(4-methylphenyl)pyrimidin-4-amine, CNN, (VIIb), the immediate precursor of 4-(1H-benzo[d]imidazol-1-yl)-6,8,11-trimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine, (VIIIb), the allyl group is disordered over two sets of atomic sites having occupancies of 0.688 (5) and 0.312 (5). The molecules of (III) are linked into chains by a C-H...π(pyrimidine) hydrogen bond, and those of (VIIb) are linked into complex sheets by three hydrogen bonds, one of the C-H...N type and two of C-H...π(arene) type. The molecules of the organic component in (VIIIa) are linked into a chain of rings by two C-H...π(arene) hydrogen bonds, and these chains are linked into sheets by the water components; a single weak C-H...N hydrogen bond links molecules of (VIIIc) into centrosymmetric R(10) dimers. Comparisons are made with some related compounds.